chr11-59773224-A-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004177.5(STX3):c.44A>G(p.Gln15Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00447 in 1,614,176 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0051 ( 5 hom., cov: 32)
Exomes 𝑓: 0.0044 ( 30 hom. )
Consequence
STX3
NM_004177.5 missense
NM_004177.5 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 3.95
Genes affected
STX3 (HGNC:11438): (syntaxin 3) The gene is a member of the syntaxin family. The encoded protein is targeted to the apical membrane of epithelial cells where it forms clusters and is important in establishing and maintaining polarity necessary for protein trafficking involving vesicle fusion and exocytosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0053287446).
BP6
?
Variant 11-59773224-A-G is Benign according to our data. Variant chr11-59773224-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 787544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-59773224-A-G is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00509 (776/152350) while in subpopulation AFR AF= 0.00734 (305/41580). AF 95% confidence interval is 0.00666. There are 5 homozygotes in gnomad4. There are 372 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 3 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
STX3 | NM_004177.5 | c.44A>G | p.Gln15Arg | missense_variant | 2/11 | ENST00000337979.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
STX3 | ENST00000337979.9 | c.44A>G | p.Gln15Arg | missense_variant | 2/11 | 1 | NM_004177.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00502 AC: 764AN: 152232Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00335 AC: 843AN: 251368Hom.: 2 AF XY: 0.00310 AC XY: 421AN XY: 135856
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GnomAD4 exome AF: 0.00440 AC: 6434AN: 1461826Hom.: 30 Cov.: 30 AF XY: 0.00430 AC XY: 3127AN XY: 727210
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GnomAD4 genome ? AF: 0.00509 AC: 776AN: 152350Hom.: 5 Cov.: 32 AF XY: 0.00499 AC XY: 372AN XY: 74516
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ESP6500AA
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37
ExAC
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391
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2022 | STX3: BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L
MutationTaster
Benign
D;D;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Benign
T;.;T
Sift4G
Benign
T;T;T
Polyphen
B;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at